Influenza continues to place a significant economic and human burden on the entire human population. In recent years, human infections with highly fatal H5N1 avian influenza strains in Hong Kong, Vietnam, Indonesia, and other nations have received much attention as one of the most likely sources of a potentially widespread infectious disease threat to international security. Efforts to better control annual influenza and prepare for possible pandemic influenza will require improved understanding of influenza's natural patterns of transmission and impact in the entire global community, not just the developed nations of the world. The Naval Research Laboratories are strategically located in three widely disparate locations of the world, including South America, the Middle East, and Southeast Asia. These laboratories, with support from the Infectious Disease Clinical Research Program (IDCRP) based at the Uniformed Services University, are prepared to comparatively study the natural history of the burden, transmission, and potential interventions of influenza in several countries concurrently through their regional networks; while simultaneously supporting the capabilities of the host nations to ameliorate the impact of endemic influenza, and plan effectively for future pandemic influenza. This will be through a combination of enhanced surveillance programs with expanded capabilities; along with specific intense cohort studies unique to each regional population. The coordination of collection and analysis of data, including harmonization of methods, and establishment of a central database, will be optimized through assistance from the IDCRP and Uniformed Services University, who have extensive experience in multi-center clinical research programs. PUBLIC HEALTH RELEVANCE: Efforts to better control annual influenza and prepare for possible pandemic influenza will require improved understanding of influenza's natural patterns of transmission and impact in the entire global community. The Naval Research Laboratories with support from the Infectious Disease Clinical Research Program (IDCRP) based at the Uniformed Services University, are prepared to comparatively study the natural history of the burden, transmission, and potential interventions of influenza in several countries while simultaneously supporting the capabilities of the host nations to ameliorate the impact of endemic influenza, and plan effectively for future pandemic influenza.